Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells
OBJECTIVE: It has been shown that SOCS-1 plays an important role in the proper control of cytokine/growth factor responses and acts as a tumor suppressor in acute myeloid leukemias. Therefore, the objective of the present study was to evaluate the in vitro effect of treatment with Nutlin-3, a small...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Faculdade de Medicina / USP
2014-01-01
|
Series: | Clinics |
Subjects: | |
Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322014000100068&lng=en&tlng=en |
id |
doaj-cbb75d39dcfa4779923c9f43b07e5cec |
---|---|
record_format |
Article |
spelling |
doaj-cbb75d39dcfa4779923c9f43b07e5cec2020-11-24T22:43:51ZengFaculdade de Medicina / USPClinics1980-53222014-01-01691687410.6061/clinics/2014(01)10S1807-59322014000100068Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cellsVeronica TisatoAlessia NorcioClaudio CeleghiniDaniela MilaniArianna GonelliPaola SecchieroOBJECTIVE: It has been shown that SOCS-1 plays an important role in the proper control of cytokine/growth factor responses and acts as a tumor suppressor in acute myeloid leukemias. Therefore, the objective of the present study was to evaluate the in vitro effect of treatment with Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, on the expression of the suppressor of cytokine signaling 1 in primary acute myeloid leukemia cells and in myeloid cell lines with differential p53 status. METHOD: The expression of the suppressor of cytokine signaling 1 was quantitatively analyzed by real-time PCR in myeloid p53wild-type (OCI and MOLM) and p53null HL-60, leukemic cell lines, in patient-derived acute myeloid leukemia blasts, and in primary normal cell types, such as macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependence of the suppressor of cytokine signaling 1 upregulation that is induced by Nutlin-3 was analyzed in experiments performed using siRNA for p53, while the functional upregulation of the suppressor of cytokine signaling 1 was analyzed by assessing the levels of phosphorylated STAT-3. RESULTS: Nutlin-3 significantly upregulated the transcription of the suppressor of cytokine signaling 1 in p53wild-type OCI and MOLM but not in p53deleted p53null HL60, myeloid leukemic cell lines, as well as in primary acute myeloid leukemia blasts. Conversely, and somewhat unexpectedly, Nutlin-3 did not modulate the suppressor of cytokine signaling 1 expression in primary normal macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependent upregulation of the suppressor of cytokine signaling 1 by Nutlin-3 was associated with the downregulation of phosphorylated STAT-3, a major molecular target of the suppressor of cytokine signaling 1. CONCLUSION: Overall, our data suggest a potential role for the suppressor of cytokine signaling 1 as a therapeutic target of Nutlin-3 in p53 wild-type acute myeloid leukemias.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322014000100068&lng=en&tlng=enNutlin-3SOCS-1AML |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Veronica Tisato Alessia Norcio Claudio Celeghini Daniela Milani Arianna Gonelli Paola Secchiero |
spellingShingle |
Veronica Tisato Alessia Norcio Claudio Celeghini Daniela Milani Arianna Gonelli Paola Secchiero Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells Clinics Nutlin-3 SOCS-1 AML |
author_facet |
Veronica Tisato Alessia Norcio Claudio Celeghini Daniela Milani Arianna Gonelli Paola Secchiero |
author_sort |
Veronica Tisato |
title |
Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells |
title_short |
Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells |
title_full |
Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells |
title_fullStr |
Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells |
title_full_unstemmed |
Upregulation of SOCS-1 by Nutlin-3 in acute myeloid leukemia cells but not in primary normal cells |
title_sort |
upregulation of socs-1 by nutlin-3 in acute myeloid leukemia cells but not in primary normal cells |
publisher |
Faculdade de Medicina / USP |
series |
Clinics |
issn |
1980-5322 |
publishDate |
2014-01-01 |
description |
OBJECTIVE: It has been shown that SOCS-1 plays an important role in the proper control of cytokine/growth factor responses and acts as a tumor suppressor in acute myeloid leukemias. Therefore, the objective of the present study was to evaluate the in vitro effect of treatment with Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, on the expression of the suppressor of cytokine signaling 1 in primary acute myeloid leukemia cells and in myeloid cell lines with differential p53 status. METHOD: The expression of the suppressor of cytokine signaling 1 was quantitatively analyzed by real-time PCR in myeloid p53wild-type (OCI and MOLM) and p53null HL-60, leukemic cell lines, in patient-derived acute myeloid leukemia blasts, and in primary normal cell types, such as macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependence of the suppressor of cytokine signaling 1 upregulation that is induced by Nutlin-3 was analyzed in experiments performed using siRNA for p53, while the functional upregulation of the suppressor of cytokine signaling 1 was analyzed by assessing the levels of phosphorylated STAT-3. RESULTS: Nutlin-3 significantly upregulated the transcription of the suppressor of cytokine signaling 1 in p53wild-type OCI and MOLM but not in p53deleted p53null HL60, myeloid leukemic cell lines, as well as in primary acute myeloid leukemia blasts. Conversely, and somewhat unexpectedly, Nutlin-3 did not modulate the suppressor of cytokine signaling 1 expression in primary normal macrophages, endothelial cells, and bone marrow mesenchymal stem cells. The p53-dependent upregulation of the suppressor of cytokine signaling 1 by Nutlin-3 was associated with the downregulation of phosphorylated STAT-3, a major molecular target of the suppressor of cytokine signaling 1. CONCLUSION: Overall, our data suggest a potential role for the suppressor of cytokine signaling 1 as a therapeutic target of Nutlin-3 in p53 wild-type acute myeloid leukemias. |
topic |
Nutlin-3 SOCS-1 AML |
url |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322014000100068&lng=en&tlng=en |
work_keys_str_mv |
AT veronicatisato upregulationofsocs1bynutlin3inacutemyeloidleukemiacellsbutnotinprimarynormalcells AT alessianorcio upregulationofsocs1bynutlin3inacutemyeloidleukemiacellsbutnotinprimarynormalcells AT claudioceleghini upregulationofsocs1bynutlin3inacutemyeloidleukemiacellsbutnotinprimarynormalcells AT danielamilani upregulationofsocs1bynutlin3inacutemyeloidleukemiacellsbutnotinprimarynormalcells AT ariannagonelli upregulationofsocs1bynutlin3inacutemyeloidleukemiacellsbutnotinprimarynormalcells AT paolasecchiero upregulationofsocs1bynutlin3inacutemyeloidleukemiacellsbutnotinprimarynormalcells |
_version_ |
1725694203223080960 |